The objectives of the proposed research are to analyze the functional significance of molecular changes which have occurred during evolution. The primary method of approach involves comparisons of nucleic acids of species in the genus Drosophila. Examples of the kinds of molecular changes that will be quantitated in different species include genome size; genome complexity (intragenome homology); rates of fixation of nucleotide substitutions; relationship between chromatid synapsis and nucleotide substitutions. The question of significance will be explored by correlating these molecular changes with gene function. Groupings within which correlations will be sought include genetic linkage, chromosome regions (heterochromatin-euchromatin distinctions), types of gene expression (kinds of products) and time of genetic activity during development. A prototype will be karyotype evolution in Drosophila. The quantitative nucleotide changes will be analyzed within the framework of karyotype stability. The expectation is that the basis of this stability will provide insight into the questions of interactions among linked genes, and the kinds of restrictions and selection which operate during evolution.